Our goal is to understand how the cellular response to growth hormone is initiated and regulated in target cells. The initiating step in hormone action is binding to membrane receptors. Elucidation of the molecular basis of growth hormone action therefore requires the isolation and purification of this receptor. Growth hormone possesses insulin-like and anti-insulin actions. Growth hormone and insulin each increase the phosphorylation of a protein of Mr 46,000. Pre-exposure to growth hormone decreases the number of insulin receptors on hepatocytes. The role of these processes in potentiating the actions of growth hormone will be characterized. Growth hormone action in cells is regulated by the affinity state of the receptor and the number of receptors on the cell surface. We will characterize the mechanisms that mediate the up- and down-regulation of the growth hormone receptor and determine if a relationship exists between receptor affinity state and receptor activity.